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ZIRC
ZFIN ID: ZDB-PUB-110914-4
Semaphorin-PlexinD1 Signaling Limits Angiogenic Potential via the VEGF Decoy Receptor sFlt1
Zygmunt, T., Gay, C.M., Blondelle, J., Singh, M.K., Flaherty, K.M., Means, P.C., Herwig, L., Krudewig, A., Belting, H.G., Affolter, M., Epstein, J.A., and Torres-Vazquez, J.
Date: 2011
Source: Developmental Cell   21(2): 301-314 (Journal)
Registered Authors: Affolter, Markus, Belting, Heinz-Georg Paul (Henry), Epstein, Jonathan A., Gay, Carl Michael, Torres-Vazquez, Jesus, Zygmunt, Tomasz
Keywords: none
MeSH Terms:
  • Angiogenesis Inhibitors/pharmacology
  • Animals
  • Animals, Genetically Modified
  • Aorta/anatomy & histology
  • Aorta/embryology
  • Cell Movement/drug effects
  • Cell Movement/genetics
  • Cell Transplantation/physiology
  • Embryo, Nonmammalian
  • Endothelial Cells/cytology
  • Endothelial Cells/drug effects
  • Endothelial Cells/physiology*
  • Endothelium/cytology
  • Endothelium/embryology
  • Endothelium/metabolism
  • Gene Expression Regulation, Developmental/drug effects
  • Gene Expression Regulation, Developmental/genetics
  • In Vitro Techniques
  • Indoles/pharmacology
  • Luminescent Proteins/genetics
  • Molecular Sequence Data
  • Neovascularization, Physiologic/genetics
  • Neovascularization, Physiologic/physiology*
  • Oligodeoxyribonucleotides, Antisense/pharmacology
  • Pyrroles/pharmacology
  • Quinoxalines/pharmacology
  • RNA, Messenger/metabolism
  • Receptors, Cell Surface/genetics
  • Receptors, Cell Surface/metabolism*
  • Receptors, Notch/genetics
  • Receptors, Notch/metabolism
  • Semaphorins/genetics
  • Semaphorins/metabolism*
  • Signal Transduction/drug effects
  • Signal Transduction/physiology*
  • Thiazolidinediones/pharmacology
  • Vascular Endothelial Growth Factor Receptor-1/deficiency
  • Vascular Endothelial Growth Factor Receptor-1/metabolism*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 21802375 Full text @ Dev. Cell
FIGURES
ABSTRACT
Sprouting angiogenesis expands the embryonic vasculature enabling survival and homeostasis. Yet how the angiogenic capacity to form sprouts is allocated among endothelial cells (ECs) to guarantee the reproducible anatomy of stereotypical vascular beds remains unclear. Here we show that Sema-PlxnD1 signaling, previously implicated in sprout guidance, represses angiogenic potential to ensure the proper abundance and stereotypical distribution of the trunk's segmental arteries (SeAs). We find that Sema-PlxnD1 signaling exerts this effect by antagonizing the proangiogenic activity of vascular endothelial growth factor (VEGF). Specifically, Sema-PlxnD1 signaling ensures the proper endothelial abundance of soluble flt1 (sflt1), an alternatively spliced form of the VEGF receptor Flt1 encoding a potent secreted decoy. Hence, Sema-PlxnD1 signaling regulates distinct but related aspects of angiogenesis: the spatial allocation of angiogenic capacity within a primary vessel and sprout guidance.
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